Cargando…

Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the p...

Descripción completa

Detalles Bibliográficos
Autores principales: Niedermann, Gabriele, Grimm, Rudolf, Geier, Elke, Maurer, Martina, Realini, Claudio, Gartmann, Christoph, Soll, Jürgen, Omura, Satoshi, Rechsteiner, Martin C., Baumeister, Wolfgang, Eichmann, Klaus
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198974/
https://www.ncbi.nlm.nih.gov/pubmed/9221750
_version_ 1782148104700559360
author Niedermann, Gabriele
Grimm, Rudolf
Geier, Elke
Maurer, Martina
Realini, Claudio
Gartmann, Christoph
Soll, Jürgen
Omura, Satoshi
Rechsteiner, Martin C.
Baumeister, Wolfgang
Eichmann, Klaus
author_facet Niedermann, Gabriele
Grimm, Rudolf
Geier, Elke
Maurer, Martina
Realini, Claudio
Gartmann, Christoph
Soll, Jürgen
Omura, Satoshi
Rechsteiner, Martin C.
Baumeister, Wolfgang
Eichmann, Klaus
author_sort Niedermann, Gabriele
collection PubMed
description To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH(2) and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.
format Text
id pubmed-2198974
institution National Center for Biotechnology Information
language English
publishDate 1997
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21989742008-04-16 Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System Niedermann, Gabriele Grimm, Rudolf Geier, Elke Maurer, Martina Realini, Claudio Gartmann, Christoph Soll, Jürgen Omura, Satoshi Rechsteiner, Martin C. Baumeister, Wolfgang Eichmann, Klaus J Exp Med Article To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH(2) and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules. The Rockefeller University Press 1997-07-21 /pmc/articles/PMC2198974/ /pubmed/9221750 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Niedermann, Gabriele
Grimm, Rudolf
Geier, Elke
Maurer, Martina
Realini, Claudio
Gartmann, Christoph
Soll, Jürgen
Omura, Satoshi
Rechsteiner, Martin C.
Baumeister, Wolfgang
Eichmann, Klaus
Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title_full Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title_fullStr Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title_full_unstemmed Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title_short Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
title_sort potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198974/
https://www.ncbi.nlm.nih.gov/pubmed/9221750
work_keys_str_mv AT niedermanngabriele potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT grimmrudolf potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT geierelke potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT maurermartina potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT realiniclaudio potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT gartmannchristoph potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT solljurgen potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT omurasatoshi potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT rechsteinermartinc potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT baumeisterwolfgang potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem
AT eichmannklaus potentialimmunocompetenceofproteolyticfragmentsproducedbyproteasomesbeforeevolutionofthevertebrateimmunesystem